Simulated Injuries of the Sheep Ossicular Chain: Correlations With Their Radiological Images.

Hypothesis We hypothesized that a sheep temporal bone would be a suitable model to study correlations between simulated middle ear injuries and their radiological appearances. Simulated ossicular chain injuries correlate well with their radiological images, and post-processing techniques provide optimal visualization of the sheep ossicles. Background The subtle ossicular trauma may be difficult to assess due to the small size of the structures. The precise radiological and clinical correlations of the ossicular injuries are not well documented. Methods The most common traumatic ossicular chain injuries were systematically simulated in the sheep temporal bone model. The images of the temporal bones were obtained with a high-resolution computed tomography scanner. The values of the dislocations were measured from the obtained images as well as in the temporal bones using calipers. Two observers independently evaluated the fine structures of the auditory ossicles using oblique multiplanar reconstructions (MPRs) and maximum intensity projections (MIPs). All segments of the facial nerve were also visualized. Results Optimal visualization planes of the sheep's middle ear joints have been obtained. The coincidence of simulated ossicular injuries in the specimens and MIPs was 40%. All structures of the ossicular chain were clearly distinguished except for the stapes footplate. Evaluation of the traumatic changes of the incudostapedial joint was challenging. Conclusions The sheep temporal bone is a suitable model for studying the correlations between pathological alterations in the ossicular chain and their radiological appearances. The post-processing MIP technique provides a more accurate and easier diagnosis of traumatic ossicular chain injuries than MPRs alone.

Tumor Treating Fields (TTFields) Reversibly Permeabilize the Blood-Brain Barrier In Vitro and In Vivo.

Despite the availability of numerous therapeutic substances that could potentially target CNS disorders, an inability of these agents to cross the restrictive blood-brain barrier (BBB) limits their clinical utility. Novel strategies to overcome the BBB are therefore needed to improve drug delivery. We report, for the first time, how Tumor Treating Fields (TTFields), approved for glioblastoma (GBM), affect the BBB's integrity and permeability. Here, we treated murine microvascular cerebellar endothelial cells (cerebEND) with 100-300 kHz TTFields for up to 72 h and analyzed the expression of barrier proteins by immunofluorescence staining and Western blot. In vivo, compounds normally unable to cross the BBB were traced in healthy rat brain following TTFields administration at 100 kHz. The effects were analyzed via MRI and immunohistochemical staining of tight-junction proteins. Furthermore, GBM tumor-bearing rats were treated with paclitaxel (PTX), a chemotherapeutic normally restricted by the BBB combined with TTFields at 100 kHz. The tumor volume was reduced with TTFields plus PTX, relative to either treatment alone. In vitro, we demonstrate that TTFields transiently disrupted BBB function at 100 kHz through a Rho kinase-mediated tight junction claudin-5 phosphorylation pathway. Altogether, if translated into clinical use, TTFields could represent a novel CNS drug delivery strategy.